Effect of each guanidinium group on the RNA recognition and cellular uptake of Tat-derived peptides
Journal
Bioorganic and Medicinal Chemistry
Journal Volume
22
Journal Issue
11
Pages
3016-3020
Date Issued
2014
Author(s)
Abstract
The six arginine (Arg) residues in the human immunodeficiency virus transactivator of transcription protein (HIV Tat protein) basic region (residues 47-57) are crucial for two bioactivities: RNA recognition and cellular uptake. Herein, we report a systematic study to investigate the role of the guanidinium group on Arg at each position in Tat-derived peptides for the two bioactivities. Tat-derived peptides, in which each guanidinium-bearing arginine was replaced with a urea-bearing citrulline (Cit) or an ammonium-bearing Lys, were synthesized by solid phase peptide synthesis. RNA recognition of the peptides was studied by electrophoretic mobility shift assays, and cellular uptake into Jurkat cells was determined by flow cytometry. Our results showed that removing the positive charge and altering the hydrogen bonding capacity of Arg affect the two biological functions differently. Furthermore, the effects are position dependent. These findings should be useful for the development of functional molecules containing guanidinium, urea, and ammonium groups for RNA recognition to affect biological processes and for cellular uptake for drug delivery. ? 2014 Elsevier Ltd. All rights reserved.
Subjects
Arginine; Cellular uptake; Guanidinium group; RNA recognition; Tat-derived peptide
SDGs
Other Subjects
ammonia; arginine; citrulline; guanidine; lysine; Tat derived peptide; transactivator protein; unclassified drug; urea; guanidine; peptide; transactivator protein; virus RNA; amino acid composition; article; binding affinity; cell transport; concentration response; controlled study; flow cytometry; gel mobility shift assay; human; human cell; hydrogen bond; jurkat cell line; molecular recognition; peptide synthesis; protein motif; protein RNA binding; solid phase synthesis; chemistry; metabolism; Human immunodeficiency virus; Flow Cytometry; Guanidine; Humans; Jurkat Cells; Peptides; RNA, Viral; tat Gene Products, Human Immunodeficiency Virus
Type
journal article